The Middle Atlantic Region consortium proposes to establish a Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (RCE), whose theme is "Defense against Bioterror and Emerging Infection Agents." The proposed Research Projects are: 1) Anthrax (new Bacillus anthracis antigens, tested in animal models; compounds to impede anthrax infection; mouse model for imaging germination and bacterial distribution; development of a mucosal live vector prime/parenteral boost anthrax vaccine); 2) Hemorrhagic Fever and other Emerging Viruses (identification/characterization of neutralizing human monoclonal antibodies reactive to functionally important determinants on Henipaviruses, Bunyaviruses, West Nile, Ebola and Marburg); 3) Poxviruses (subunit variola vaccine; identification of new targets of neutralizing antibody and of vaccinia immune globulin; and development of a mouse ectromelia virus model of smallpox pathogenesis/prevention); 4) Tularemia (conjugate tularemia vaccine; study possible therapy of F. tularensis infection using reagents already under clinical testing for sepsis; evaluate currently available bisphosphonate drugs as a first line of defense for individuals exposed to F. tularensis; attenuated, live-vector tularemia vaccine); 5) Low-Dose Enteric Pathogens (role of type 1 Cryptosporidium parvum candidate genes in pathogenesis/susceptibility to infection, as a prelude to vaccine development; Shigella dysenteriae 1 and EHEC vaccines; novel therapeutics for EHEC disease; diagnostics for detection of these pathogens in water, food, and environmental specimens); 6) Public Health Response Research (needle-free immunization and vaccine-adjuvanting strategies; immunogenetics of human immune response to smallpox vaccine; innovative diagnostic platforms for routine clinical use and in known or suspected bioterror events). Three Career Development Projects (to train the next generation of biodefense investigators) and 4 Developmental Projects (high-risk projects on biodefense agents) will be funded per year. Training will include a Media Training Course; a short course in "GMP Production and Process Development" (in collaboration with Aventis Pasteur Vaccines and Merck Vaccines); a Category A Bioterror Agent Clinical Surveillance Course; a "hands-on" course on working in BSL-3 facilities; and travel awards for RCE scientists and trainees to visit other RCE labs to learn techniques or perform collaborative experiments.